Homicide mortality remains a major public health problem in Brazil, especially among young adult males. The aim of this study was to assess the homicide mortality risk (HMR) among males aged 20 to 39, and its association with selected socio-demographic characteristics of the Brazilian municipalities. This is an ecologic study in which all the municipalities in Brazil were the unit of analysis. Time trends (from 1999-2002) and adjusted associations between HMR and socio-demographic characteristics of municipalities were estimated in a cross-sectional analysis for 2007-2010 in this study. Between 1999-2002 and 2007-2010, an increasing trend of mean HMR rates from 22.7 to 35.5 per 100,000 inhabitants was observed in Brazil. In 2007-2010, HMR rates were significantly higher (p<0.001) in the largest cities, with higher fertility rates, lower literacy rates, higher social inequality (as estimated by the 20/40 income ratio) and more-urbanized municipalities. Considering the proportion of low income population and the average per capita income, associations with HMR identified greater risks in the intermediary categories of these independent variables. Findings from this study may support the implementation of focal policies directed to more vulnerable municipalities.